Upregulation of bacterial and fungal pathogen sensing genes in preinvasive colorectal lesions in African Americans compared to Caucasian Americans

Background: Colorectal cancer (CRC) incidence and mortality are higher for African Americans (AAs) than Caucasian Americans (CAs). Variation in tumor immune responses by race appears to be important for prognosis. However, few studies have compared immune gene expression in preinvasive lesions where prevention may be possible. Methods: The immune gene expression of 95 cases of colorectal adenomas (AA 47, CA 48) excised via sigmoidoscopy or colonoscopy with polypectomy between October 2012 and May 2016 was assessed using the NanoString nCounter platform using the immunology v2 panel (n=579 genes). Data were analyzed using a NanoStringDiff R package, implementing negative binomial regression models of gene expression as the dependent variable and race group (AA vs. CA) as the primary predictor variable. Models were adjusted for age, sex, location within the colon, histology, and degree of dysplasia. Results: In AAs vs. CAs, 24 immune genes were up-regulated, while 11 genes were down-regulated (for each gene, p<0.01). Compared to CAs, genes overexpressed in AAs suggest more robust antibacterial and antifungal responses (e.g., IL17F, IL21, AIRE, IL1A, GATA3, MARCO, FCGR1A). Enhanced expression of terminal components of the complement pathway C8B and C9 further support an increased effector response in AAs. Additionally, genes related to wound healing (e.g., GP1BB, XCL1) were overexpressed in AAs. Genes associated with stimulation of cytotoxic responses (NCR1, HLADRB1), complement activation through lectin-related pathways (ITLN2, MBL2), and recruitment and function of innate immune cells (IL8 and IL6) had lower expression in AAs vs. CAs. Conclusion: Our results suggest that preinvasive neoplasms in AAs vs. CAs display a gene expression that is suggestive of heightened sensing of bacterial and fungal commensals, which may potentially inflame local tissues and support tumor progression. Understanding the molecular differences in early tumorigenesis between AAs vs. CAs may help inform prevention interventions to address racial disparities. Citation Format: Silvia Guglietta, Lauren R. Fanning, Alexandria G. Cousart, Kent E. Armeson, Zequn Sun, David N. Lewin, J Grant Brazeal, Dongjun Chung, Alexander V. Alekseyenko, Kristin Wallace. Upregulation of bacterial and fungal pathogen sensing genes in preinvasive colorectal lesions in African Americans compared to Caucasian Americans [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-196.